The effect of prostaglandins (PGE1, PGE2, PGF1Alpha, PGF2Alpha, PGD2) on adenylate cyclase (AC) was investigated in cerebromicrovascular smooth muscle and glial cell cultures. PGE1 and PGE2, in contrast to PGF1 and PGF2, stimulated cAMP formation in both cell types. The smooth muscle AC system showed a greater affinity for E-type prostaglandins than the AC system in glial cells. Most importantly, a dose-dependent PGI2, but not PGD2 enhancement of cAMP formation, was manifested in smooth muscle while a reverse AC reactivity of PGI2 and PGD2 was seen in glial cells. These findings indicate that the prostaglandin receptors linked to AC are distinct in each cell type.